Methamphetamine (MA) dependence is a significant health problem in South Africa and the U.S. In South Africa, a shift in policy focus is required away from allocating health resources primarily to HIV/AIDS and TB and toward the financial, social and personal consequences of untreated stimulant addiction. In response to PAR 14-331, this application proposes to build capacity for a new linkage of productive teams of clinical researchers at UCLA and the University of Cape Town to conduct studies on the neurobiological foundation of treatment for stimulant dependence. The research direction is innovative in linking findings from neuroscience with clinical outcomes using contingency management (CM) to identify changes in brain structure and function that emerge during purely behavioral therapy. The knowledge gained may guide development of optimally effective behavioral and/or medication therapies. The application design will correlate MA-abstinence outcomes from an 8-week program of voucher-based incentives using an escalating schedule for 30 treatment-seeking, MA-dependent individuals with scores on tasks of working memory and assessments of neuropsychological and demographic status. At the beginning and end of the CM program, participants will participate in MRI scans while performing a working memory task, and will complete a battery of select neurocognitive and psychological assays to address two specific aims: (1) to determine whether changes in neural function within front striatal circuitry from baseline to end of the 8- week CM program are associated with parallel changes in measures of cognitive control and impulsivity and with MA abstinence outcomes; (2) to determine whether structural changes in front striatal circuitry over the 8-week CM intervention correspond with neurocognitive, psychological and MA abstinence measures. Findings from this study will describe associations between: (1) functional and structural indices of brain areas that support working memory, cognitive control/inhibition; (2) performance on select neurocognitive and psychological assessments; and (3) associations between these with MA abstinence outcomes. Study activities and the neuroscience data generated will provide preliminary data for a larger, adequately powered study that will test ways to optimize behavioral therapies for treating stimulant use disorder.